Molecular Magnetic Resonance Imaging Probes Based on Ln3+ Complexes

For almost three decades, the application of Gd3+ complexes as contrast-enhancing agents has largely contributed to the successful use of magnetic resonance imaging (MRI) both in the clinics and in biomedical research. More recently, the emergence of paramagnetic Chemical Exchange Saturation Transfer (ParaCEST) agents, most often based on lanthanide chelates, opened new possibilities to create MRI contrast. Via a judicious ligand design, the efficacy of Gd3+ complexes or the CEST effect of ParaCEST agents can be modulated by a variety of physical-chemical parameters (pH, temperature, ion concentration, etc.) or by interaction with biomarkers. This allows developing responsive probes, capable of reporting on different properties of the surrounding tissue. We survey recent contributions in the field of responsive probes for detection of enzymes, biologically important cations, or neurotransmitters. The specificity of a molecular probe can be improved by selectively delivering it to a specific target. Discrete MR probes can be adapted to visualize abundant targets. An important challenge is to retain the affinity of the vector for its target upon conjugation to paramagnetic chelates. These issues are discussed in the context of imaging of amyloid aggregates by Gd3+ complexes. To ascertain MRI findings, the possible detection of the probe in optical imaging is often explored. For this, imaging agents need to combine features required by MRI and optical imaging. We review approaches including both small molecular probes and nanoparticles. Finally, different nonconventional systems such as metal-organic frameworks, rotaxanes, or zeolites are discussed as potential MRI probes.